The formation of hydrogen peroxide and free radicals from glutathione (GSH) is dependent on the activity of g-glutamyltranspetidase (GGT), an enzyme that is frequently present in high concentrations in prenoplastic cells. GSH, in the presence of GGT, can induce lipid peroxidaticn in vitro, using linclenic acid linoleic acid as substrates. and in situ in cultured human hepatoma cells. Mutagenicity of Salmonella and peroxidation occurs in the presence of physiological concentrations of GSH, iron and copper, and endogenous chelators (citrate, ADP, transferrin, ceruloplasm). Unlike the mutagenic effect of GSH which is mediated through the formation of H2O2, lipid peroxidation appears to be effected through a free radical reaction, without the intermediate formation of H2O2. The effects of antioxidants and free radical scavengers on mutagenicity and lipid peroxidation induced by other sulfhydryls, such as D- and L-cysteine and D- and L-penicillamine are being studied. Studies are in progress to test whether lipid peroxidation can be induced in GGT-rich preneoplastic foci in rodents when challenged with GSH.